Matrix metalloproteinases (MMP) are a group of metalloproteinases and it is a generic term for proteinases that include a metal ion in its active center. More than 20 types of MMPs are known, such as MMP1, MMP2, MMP3, MMP7, MMP8, MMP9, and MMP10. MMPs exhibit functions such as degradation of extracellular matrix including collagen, proteoglycan, elastin, etc., degradation of proteins expressed on cell surfaces, and processing of physiologically-active substances. There is a report of a transgenic (TG) non-human mammal (mouse) that expresses human MMP1 (hMMP1) (Non-Patent Document 1). Although this TG mouse expressed hMMP1 in lung tissue, expression in organs of the entire body was not observed. In addition, TG non-human mammals that systemically express hMMP2 are not known.
Concurrently, chronic obstructive pulmonary disease (COPD) is a general term that consolidates the disease concept that has been pathologically referred to as emphysema and the disease concept that has been clinically referred to as chronic bronchitis. These concepts were specified in an international guideline (GOLD) in 2001 and in clinical practice guidelines of the Japanese Respiratory Society. In addition, these disease concepts have been formalized at the levels of Japanese and international academic societies. As one of the COPDs, emphysema is a disease associated with destructive changes in the alveolar walls, and exhibits a condition in which aerated sections ranging from the respiratory tract and the terminal bronchiole to the periphery are abnormally enlarged. Although the progression of COPD is slow, COPD further progresses to cor pulmonale if left untreated. COPD is a disease that develops after a history of smoking for 20 years or more. In Japan, the number of deaths due to COPD in 2011 was 16,639, and continues to increase.